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Summary: B‐cell content in the tumour microenvironment (TME) of classic Hodgkin lymphoma (HL) is known to be associated with prognosis. Here we demonstrate that whole slide image analysis using routinely available slides predicts outcomes in patients treated with ABVD in a prospective trial with a high B‐cell content being associated with a favourable prognosis. B cells in the TME did not correlate with B cells in peripheral blood. In the TME maturation, stages of B cells (naive and memory) were consistent. However, we detected down‐regulation of CD73 in HL with low B cells suggestive of an antibody‐independent function of B cells in the TME of HL. [ABSTRACT FROM AUTHOR]

Objectives: Patients with classical Hodgkin lymphoma (cHL) relapsing after second‐line therapy have a dismal prognosis and novel approaches are required for this patient group. Based on promising (pre‐)clinical data and the favourable toxicity profile, we performed a phase II clinical trial with the JAK inhibitor ruxolitinib in patients with relapsed or refractory cHL (r/r cHL). Methods: Patients ≥18 years with histologically confirmed r/r cHL who failed second‐line treatment were included. Ruxolitinib was given orally at a dose of 25 mg twice daily in continuous 28‐day cycles until progression or unacceptable toxicity. Primary endpoint was the PET/CT‐based overall response rate (ORR; complete response (CR) or partial response (PR)) after 2 cycles; secondary endpoints included progression‐free (PFS) and overall survival (OS) as well as feasibility. The Jericho Trial adopted a 2‐stage phase 2 design (Simon 1989). Results: Among the 12 included patients in stage 1, 2 had a PR, 3 had a stable disease (SD) and 6 had progressive disease (PD) after two treatment cycles (ORR: 2/12 evaluable patients, 16.7%). Median PFS was 3.6 months, the 1‐year OS estimate was 50.6% (median not reached). The toxicity profile was favourable with only one grade IV adverse event (7.1%) reported. Conclusion: Ruxolitinib exhibited a favourable side effect profile but modest activity in r/r cHL. Although the formal stopping criterion after stage 1 was not met, the trial did not continue to stage 2 due to the low response and PFS rates observed in stage 1. [ABSTRACT FROM AUTHOR]

Summary: Reinduction chemotherapy followed by high‐dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second‐line standard of care for transplant‐eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high‐dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant‐eligible patients aged 18–60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase‐I‐part) was administered on day 0–13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end‐point of computed tomography (CT)‐based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT‐based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end‐point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy. [ABSTRACT FROM AUTHOR]

Summary: We retrospectively investigated histopathological growth patterns in individuals with advanced nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) treated within the randomized HD18 study. In all, 35/60 patients (58%) presented with atypical growth patterns. Patients with atypical growth patterns more often had stage IV disease (P = 0·0354) and splenic involvement (P = 0·0048) than patients with typical growth patterns; a positive positron emission tomography after two cycles of chemotherapy (PET‐2) tended to be more common (P = 0·1078). Five‐year progression‐free survival [hazard ratio (HR) = 0·86; 95% confidence interval (CI) = 0·49–1·47] and overall survival (HR = 0·85; 95% CI = 0·49–1·51) did not differ between the groups after study treatment with PET‐2‐guided escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). Thus, advanced NLPHL is often associated with atypical growth patterns but their prognostic impact is compensated by PET‐2‐guided escalated BEACOPP. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to determine the effectiveness of brentuximab vedotin (BV) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) in the clinical practice setting using most recent results. A total of 32 observational studies reporting on treatment patterns, overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and adverse events were found. After four cycles, a random-effect model yielded pooled ORR and CR rates of 62.6% (95% confidence interval (CI): 56.0–68.9; I2 = 9.7%) and 32.9% (95% CI, 20.8–46.3, I2 = 64.8%), respectively. Regarding survival, 1-year, 2-year, and 5-year PFS ranged from 52.1% to 63.2%, 45.2% to 56.2%, and 31.9% to 33.0%, respectively. OS rates were 68.2–82.7%, 58.0–81.9%, and 58.0–62.0%, respectively. Most common adverse events were hematological toxicities (neutropenia: 13.3–23%, anemia: 8.8–39.0%, and thrombocytopenia: 4–4.6%), and grade ≥3 peripheral neuropathy (3.3–7.3%). This study supports the effectiveness and safety of BV in R/R cHL patients in the real-world setting. [ABSTRACT FROM AUTHOR]

Patients with classical Hodgkin lymphoma (cHL) typically receive first-line chemotherapy or chemoradiotherapy, and cure rates are high [[1]]. When response was evaluated by prior lines of therapy, ORR was 79.4% (95% CI, 67.3-88.5) among patients who had received at least three prior therapies ( I n i = 63) and 100.0% (95% CI, 63.1-100.0) among patients who had received fewer than three prior therapies ( I n i = 8). However, for patients who have primary refractory cHL that does not respond to salvage chemotherapy or for patients who are ineligible for transplantation because of comorbidity, pembrolizumab could be an effective treatment option. [Extracted from the article]

What is it that we actually see when looking at PET (positron emission tomography)-positive signals in Hodgkin lymphoma (HL)? Thus, the question of how to manage PET-positive lesions at the end of frontline therapy in HL is indeed crucial, because undertreating a disease that can be cured with firstline treatment in 80-90% of cases must definitely be avoided. As a result the authors concluded that it may not always be decisive to perform a biopsy for PET-positive residual mediastinal tissue after frontline therapy and that it was safe and appropriate to first closely observe asymptomatic patients instead of directly intensifying treatment. In the GHSG HD15 trial Engert et al. assessed whether administering RT only to patients with persistent PET-positive residues after chemotherapy was justifiable compared to earlier trials where irradiation was given to all initial bulky findings and all residual disease. [Extracted from the article]

In KEYNOTE-087, pembrolizumab had a 69% overall response rate and acceptable safety in patients with relapsed/refractory classical Hodgkin lymphoma (rrHL). We assessed health-related quality of life (HRQoL) in KEYNOTE-087. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire 3-level version (EQ-5D) were administered to 206 patients across three cohorts defined by lymphoma progression after: (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV) (n = 69); (2) salvage chemotherapy and BV (n = 79); and (3) ASCT without post-transplantation BV (n = 58). Compliance/completion rates were ≥90% at week 12 and ≥70% at week 24. QLQ-C30 global health status/QoL and EQ-5D visual analog scale scores showed mean increases from baseline in overall health at all assessed timepoints. With few exceptions, mean improvements from baseline to weeks 12 and 24 in QLQ-C30 functional and symptom scores occurred in all cohorts. Clinicaltrials.gov identifier: NCT02453594. [ABSTRACT FROM AUTHOR]

We examined real-world data on management of relapsed/refractory Hodgkin lymphoma (R/R HL) in five European countries and the consistency of these data with guideline recommendations. Retrospective clinical and epidemiologic data for 509 patients with R/R HL treated between January 2014 and March 2015 were collected at centers in France, Germany, Italy, Spain, and the United Kingdom. Mean age was 46.3 years; 73.3% were receiving second-line therapy for a first relapse during the reporting period. Most patients received ABVD as front-line chemotherapy, except in Germany where escalated BEACOPP was used more often. The proportion of patients receiving stem cell transplantation (SCT) was 44%; 85% of transplants occurred at first relapse. Brentuximab vedotin (BV) was usually administered after autologous SCT, and was initiated for 65% of patients following SCT failure. Our findings suggest that R/R HL management across these countries is broadly consistent with guideline recommendations and that BV is well-integrated into treatment pathways. [ABSTRACT FROM AUTHOR]

The article provides information on a study which observed the link between different blood count parameters at baseline with response and progression-free survival (PFS) in relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL) patients treated with the anti-PD1 antibody, nivolumab. Topics discussed include role of eosinophils as co-effectors of the immune response, and results of the study.

Classical Hodgkin lymphoma (cHL) is the most common hematological malignancy in young adults and can be cured in most cases. However, relapsed and refractory Hodgkin lymphoma, certain patient groups, such as elderly patients, and toxicity of first-line treatment still pose significant challenges. Consequently, new treatment options are needed. Recently, many new treatment concepts have been evaluated in clinical trials. Targeted drug-antibody conjugates and immune checkpoint inhibitors have decisively changed treatment approaches. This review aims to give a comprehensive overview of novel agents in Hodgkin lymphoma that have been recently or are currently being evaluated in clinical trials. In addition to dedicated sections on brentuximab vedotin (BV) and immune checkpoint inhibitors, other emerging substances and concepts are discussed. In doing so, this review compares trial results regarding safety and efficacy. A special focus lies on the effect novel agents will have on the different treatment settings faced by clinicians involved in the treatment of Hodgkin lymphoma. [ABSTRACT FROM PUBLISHER]

Treatment for Hodgkin lymphoma is effective for about 85% of the patients. A gold-standard for the 15% of relapsing patients is still missing. High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) has shown efficacy and safety for patients, but up to date no survival benefit revealed. After systematic literature search we identified three randomised controlled trials from 1663 total hits. Meta-analysis of two trials (157 patients) showed a statistically significant increase in progression-free survival (hazard ratio 0.55, 95% confidence interval 0.35–0.86) for patients treated with HDCT and ASCT compared to conventional chemotherapy, but no difference in overall survival nor increased adverse events. The third trial (241 patients) showed an statistically significant increase in infections and 5% more treatment-related mortalities following sequential HDCT plus HDCT and ASCT compared to HDCT plus ASCT, without differences in the efficacy endpoints overall survival or progression-free survival. [ABSTRACT FROM AUTHOR]

Background: With an incidence of 2 to 3 cases per 100 000 persons per year, Hodkgin's lymphoma (HL) is rare, but nonetheless one of the most common cancers in young adults. Improved treatment has made HL curable even in advanced stages, but controversy still surrounds a number of issues in patient care. Current research focuses on the avoidance of long-term adverse effects and secondary malignancies. Methods: We selectively searched MEDLINE, CENTRAL, and the Guideline International Network for publications about HL. Two experts independently screened the retrieved publications for pertinence and extracted data from potentially relevant meta-analyses, randomized controlled trials (RCTs), and cohort studies into evidence tables. Results: 32 key questions were answered with 160 recommendations on the basis of evidence from 43 RCTs, 21 meta-analyses, and 119 cohort studies. Patients in an early stage of HL should be treated with two cycles of ABVD followed by involved-field radiotherapy (IF-RT) at a dose of 20 Gy (5-year overall survival [OS]: 94%). Patients in an intermediate (early unfavorable) stage should be treated with two cycles of BEACOPP escalated followed by two cycles of ABVD and 30 Gy IF-RT (5-year OS: 97.2%). Patients in an advanced stage should be treated with six cycles of BEACOPP escalated, and the decision whether this should be followed by consolidating radiotherapy (30 Gy) should be based on the findings of positron-emission tomography (radiate in case of PET-positive residual tumor; 5-year OS: 95.3%). Depending on the treatment regimen, there may be adverse effects including infection, leukopenia, anemia, thrombocytopenia, secondary neoplasia, and fertility disorders. Conclusion: Most questions in the treatment of HL can now be answered on the basis of sufficient evidence from the literature. This holds in particular for the potential benefit to be gained from PET, follow-up care, and lifestyle recommendations for patients. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to investigate the outcome and risk factors of patients with Hodgkin lymphoma (HL) who relapse or progress after autologous stem cell transplant (ASCT). Researchers evaluated 149 patients. They found that 75% died within 65 months after recurrence of HL following ASCT and that nearly 40% died within one year.

Doxorubicin, bleomycin, vinblastine sulfate, and dacarbazine (ABVD) is associated with severe toxicity in older patients, particularly from bleomycin-induced lung toxicity (BLT). Therefore, using bleomycin has been questioned in older Hodgkin lymphoma (HL) patients, especially in early-stage HL. We therefore analyzed feasibility, toxicity, and efficacy of ABVD or AVD in 287 older early-stage favorable HL patients. We included patients ≥60 years of age in the German Hodgkin Study Group HD10 and HD13 trials randomized to either 2 cycles of ABVD (2 x ABVD; n = 137) or AVD (23AVD; n= 82), each followed by involved-field radiotherapy (IF-RT), with patients randomized to 43ABVD1IFRT (n568). Patients' median age was 65 years (range, 60-75) with comparable patient and disease characteristics. Grade III-IV adverse event rates were similar in patients receiving 23AVD and 2 x ABVD (40% and 39%, respectively), but considerably higher in patients receiving 43ABVD (65%). Similarly, BLT was rare in patients receiving 2 x ABVD/AVD, but occurred in 7/69 (10%) of patients randomized to 43ABVD, with 3 lethal events. In conclusion, no effects of bleomycin on toxicity rates were detectable in older patients receiving 2 cycles of chemotherapy. However, we found a high risk of severe toxicity of bleomycin in older HL patients receiving more than 2 cycles of ABVD. These trials are registered at www.clinicaltrials.gov and www.isrctn.com as #NCT00265018 (HD10) and #ISRCTN63474366 (HD13). [ABSTRACT FROM AUTHOR]